document_title: Corporation

question_text: where does one look to find the powers of a corporation

text: Corporation

text: History[edit]

text: The word "corporation" derives from corpus, the Latin word for body, or a "body of people". By the time of Justinian (reigned 527–565), Roman law recognized a range of corporate entities under the names universitas, corpus or collegium. These included the state itself (the Populus Romanus), municipalities, and such private associations as sponsors of a religious cult, burial clubs, political groups, and guilds of craftsmen or traders. Such bodies commonly had the right to own property and make contracts, to receive gifts and legacies, to sue and be sued, and, in general, to perform legal acts through representatives. Private associations were granted designated privileges and liberties by the emperor.[12]

text: Entities which carried on business and were the subjects of legal rights were found in ancient Rome, and the Maurya Empire in ancient India.[13] In medieval Europe, churches became incorporated, as did local governments, such as the Pope and the City of London Corporation. The point was that the incorporation would survive longer than the lives of any particular member, existing in perpetuity. The alleged oldest commercial corporation in the world, the Stora Kopparberg mining community in Falun, Sweden, obtained a charter from King Magnus Eriksson in 1347.

text: In medieval times, traders would do business through common law constructs, such as partnerships. Whenever people acted together with a view to profit, the law deemed that a partnership arose. Early guilds and livery companies were also often involved in the regulation of competition between traders.

text: Mercantilism[edit]

text: The progenitors of the modern corporation were the chartered companies, such as the Dutch East India Company (VOC) and the Hudson's Bay Company, which were created to lead the colonial ventures of European nations in the 17th century. Acting under a charter sanctioned by the Dutch government, the Dutch East India Company defeated Portuguese forces and established itself in the Moluccan Islands in order to profit from the European demand for spices. Investors in the VOC have issued paper certificates as proof of share ownership, and were able to trade their shares on the original Amsterdam Stock Exchange. Shareholders are also explicitly granted limited liability in the company's royal charter.[28]

text: In England, the government created corporations under a royal charter or an Act of Parliament with the grant of a monopoly over a specified territory. The best-known example, established in 1600, was the East India Company of London. Queen Elizabeth I granted it the exclusive right to trade with all countries to the east of the Cape of Good Hope. Some corporations at this time would act on the government's behalf, bringing in revenue from its exploits abroad. Subsequently, the Company became increasingly integrated with English and later British military and colonial policy, just as most corporations were essentially dependent on the Royal Navy's ability to control trade routes.

text: Labeled by both contemporaries and historians as "the grandest society of merchants in the universe", the English East India Company would come to symbolize the dazzlingly rich potential of the corporation, as well as new methods of business that could be both brutal and exploitative.[29] On 31 December 1600, Queen Elizabeth I granted the company a 15-year monopoly on trade to and from the East Indies and Africa.[30] By 1711, shareholders in the East India Company were earning a return on their investment of almost 150 per cent. Subsequent stock offerings demonstrated just how lucrative the Company had become. Its first stock offering in 1713–1716 raised £418,000, its second in 1717–1722 raised £1.6 million.[31]

text: A similar chartered company, the South Sea Company, was established in 1711 to trade in the Spanish South American colonies, but met with less success. The South Sea Company's monopoly rights were supposedly backed by the Treaty of Utrecht, signed in 1713 as a settlement following the War of the Spanish Succession, which gave Great Britain an asiento to trade in the region for thirty years. In fact the Spanish remained hostile and let only one ship a year enter. Unaware of the problems, investors in Britain, enticed by extravagant promises of profit from company promoters bought thousands of shares. By 1717, the South Sea Company was so wealthy (still having done no real business) that it assumed the public debt of the British government. This accelerated the inflation of the share price further, as did the Bubble Act 1720, which (possibly with the motive of protecting the South Sea Company from competition) prohibited the establishment of any companies without a Royal Charter. The share price rose so rapidly that people began buying shares merely in order to sell them at a higher price, which in turn led to higher share prices. This was the first speculative bubble the country had seen, but by the end of 1720, the bubble had "burst", and the share price sank from £1000 to under £100. As bankruptcies and recriminations ricocheted through government and high society, the mood against corporations, and errant directors was bitter.

text: In the late 18th century, Stewart Kyd, the author of the first treatise on corporate law in English, defined a corporation as:

text: a collection of many individuals united into one body, under a special denomination, having perpetual succession under an artificial form, and vested, by policy of the law, with the capacity of acting, in several respects, as an individual, particularly of taking and granting property, of contracting obligations, and of suing and being sued, of enjoying privileges and immunities in common, and of exercising a variety of political rights, more or less extensive, according to the design of its institution, or the powers conferred upon it, either at the time of its creation, or at any subsequent period of its existence.

text: Modern company law[edit]

text: Due to the late 18th century abandonment of mercantilist economic theory and the rise of classical liberalism and laissez-faire economic theory due to a revolution in economics led by Adam Smith and other economists, corporations transitioned from being government or guild affiliated entities to being public and private economic entities free of governmental directions.[32]

text: Adam Smith wrote in his 1776 work The Wealth of Nations that mass corporate activity could not match private entrepreneurship, because people in charge of others' money would not exercise as much care as they would with their own.[33]

text: Deregulation[edit]

text: The British Bubble Act 1720's prohibition on establishing companies remained in force until its repeal in 1825. By this point, the Industrial Revolution had gathered pace, pressing for legal change to facilitate business activity.[34] The repeal was the beginning of a gradual lifting on restrictions, though business ventures (such as those chronicled by Charles Dickens in Martin Chuzzlewit) under primitive companies legislation were often scams. Without cohesive regulation, proverbial operations like the "Anglo-Bengalee Disinterested Loan and Life Assurance Company" were undercapitalised ventures promising no hope of success except for richly paid promoters.[35]

text: The process of incorporation was possible only through a royal charter or a private act and was limited, owing to Parliament's jealous protection of the privileges and advantages thereby granted. As a result, many businesses came to be operated as unincorporated associations with possibly thousands of members. Any consequent litigation had to be carried out in the joint names of all the members and was almost impossibly cumbersome. Though Parliament would sometimes grant a private act to allow an individual to represent the whole in legal proceedings, this was a narrow and necessarily costly expedient, allowed only to established companies.

text: Then, in 1843, William Gladstone became the chairman of a Parliamentary Committee on Joint Stock Companies, which led to the Joint Stock Companies Act 1844, regarded as the first modern piece of company law.[36] The Act created the Registrar of Joint Stock Companies, empowered to register companies by a two-stage process. The first, provisional, stage cost £5 and did not confer corporate status, which arose after completing the second stage for another £5. For the first time in history, it was possible for ordinary people through a simple registration procedure to incorporate.[37] The advantage of establishing a company as a separate legal person was mainly administrative, as a unified entity under which the rights and duties of all investors and managers could be channeled.

text: Limited liability[edit]

text: However, there was still no limited liability and company members could still be held responsible for unlimited losses by the company.[38] The next, crucial development, then, was the Limited Liability Act 1855, passed at the behest of the then Vice President of the Board of Trade, Mr. Robert Lowe. This allowed investors to limit their liability in the event of business failure to the amount they invested in the company – shareholders were still liable directly to creditors, but just for the unpaid portion of their shares. (The principle that shareholders are liable to the corporation had been introduced in the Joint Stock Companies Act 1844).

text: The 1855 Act allowed limited liability to companies of more than 25 members (shareholders). Insurance companies were excluded from the act, though it was standard practice for insurance contracts to exclude action against individual members. Limited liability for insurance companies was allowed by the Companies Act 1862.

text: This prompted the English periodical The Economist to write in 1855 that "never, perhaps, was a change so vehemently and generally demanded, of which the importance was so much overrated. "[39] The major error of this judgment was recognised by the same magazine more than 70 years later, when it claimed that, "[t]he economic historian of the future. . . may be inclined to assign to the nameless inventor of the principle of limited liability, as applied to trading corporations, a place of honour with Watt and Stephenson, and other pioneers of the Industrial Revolution. "[40]

text: These two features – a simple registration procedure and limited liability – were subsequently codified into the landmark 1856 Joint Stock Companies Act. This was subsequently consolidated with a number of other statutes in the Companies Act 1862, which remained in force for the rest of the century, up to and including the time of the decision in Salomon v A Salomon & Co Ltd.[41]

text: The legislation shortly gave way to a railway boom, and from then, the numbers of companies formed soared. In the later nineteenth century, depression took hold, and just as company numbers had boomed, many began to implode and fall into insolvency. Much strong academic, legislative and judicial opinion was opposed to the notion that businessmen could escape accountability for their role in the failing businesses.

text: Further developments[edit]

text: In 1892, Germany introduced the Gesellschaft mit beschränkter Haftung with a separate legal personality and limited liability even if all the shares of the company were held by only one person. This inspired other countries to introduce corporations of this kind.

text: The last significant development in the history of companies was the 1897 decision of the House of Lords in Salomon v. Salomon & Co. where the House of Lords confirmed the separate legal personality of the company, and that the liabilities of the company were separate and distinct from those of its owners.

text: In the United States, forming a corporation usually required an act of legislation until the late 19th century. Many private firms, such as Carnegie's steel company and Rockefeller's Standard Oil, avoided the corporate model for this reason (as a trust). State governments began to adopt more permissive corporate laws from the early 19th century, although these were all restrictive in design, often with the intention of preventing corporations for gaining too much wealth and power.[42]

text: New Jersey was the first state to adopt an "enabling" corporate law, with the goal of attracting more business to the state,[43] in 1896. In 1899, Delaware followed New Jersey's lead with the enactment of an enabling corporate statute, but Delaware only became the leading corporate state after the enabling provisions of the 1896 New Jersey corporate law were repealed in 1913.[42]

text: The end of the 19th century saw the emergence of holding companies and corporate mergers creating larger corporations with dispersed shareholders. Countries began enacting anti-trust laws to prevent anti-competitive practices and corporations were granted more legal rights and protections. The 20th century saw a proliferation of laws allowing for the creation of corporations by registration across the world, which helped to drive economic booms in many countries before and after World War I. Another major post World War I shift was toward the development of conglomerates, in which large corporations purchased smaller corporations to expand their industrial base.

text: Starting in the 1980s, many countries with large state-owned corporations moved toward privatization, the selling of publicly owned (or 'nationalised') services and enterprises to corporations. Deregulation (reducing the regulation of corporate activity) often accompanied privatization as part of a laissez-faire policy.

text: Ownership and control[edit]

text: A corporation is, at least in theory, owned and controlled by its members. In a joint-stock company the members are known as shareholders and each of their shares in the ownership, control, and profits of the corporation is determined by the portion of shares in the company that they own. Thus a person who owns a quarter of the shares of a joint-stock company owns a quarter of the company, is entitled to a quarter of the profit (or at least a quarter of the profit given to shareholders as dividends) and has a quarter of the votes capable of being cast at general meetings.

text: In another kind of corporation, the legal document which established the corporation or which contains its current rules will determine who the corporation's members are. Who a member is depends on what kind of corporation is involved. In a worker cooperative, the members are people who work for the cooperative. In a credit union, the members are people who have accounts with the credit union.[44]

text: The day-to-day activities of a corporation are typically controlled by individuals appointed by the members. In some cases, this will be a single individual but more commonly corporations are controlled by a committee or by committees. Broadly speaking, there are two kinds of committee structure.

text:
A single committee known as a board of directors is the method favored in most common law countries. Under this model, the board of directors is composed of both executive and non-executive directors, the latter being meant to supervise the former's management of the company.
A two-tiered committee structure with a supervisory board and a managing board is common in civil law countries.[45]

tag: ul

text: Formation[edit]

text: Historically, corporations were created by a charter granted by government. Today, corporations are usually registered with the state, province, or national government and regulated by the laws enacted by that government. Registration is the main prerequisite to the corporation's assumption of limited liability. The law sometimes requires the corporation to designate its principal address, as well as a registered agent (a person or company designated to receive legal service of process). It may also be required to designate an agent or other legal representative of the corporation.[citation needed]

text: Generally, a corporation files articles of incorporation with the government, laying out the general nature of the corporation, the amount of stock it is authorized to issue, and the names and addresses of directors. Once the articles are approved, the corporation's directors meet to create bylaws that govern the internal functions of the corporation, such as meeting procedures and officer positions.[citation needed]

text: The law of the jurisdiction in which a corporation operates will regulate most of its internal activities, as well as its finances. If a corporation operates outside its home state, it is often required to register with other governments as a foreign corporation, and is almost always subject to laws of its host state pertaining to employment, crimes, contracts, civil actions, and the like.[citation needed]

text: Naming[edit]

text: Corporations generally have a distinct name. Historically, some corporations were named after their membership: for instance, "The President and Fellows of Harvard College". Nowadays, corporations in most jurisdictions have a distinct name that does not need to make reference to their membership. In Canada, this possibility is taken to its logical extreme: many smaller Canadian corporations have no names at all, merely numbers based on a registration number (for example, "12345678 Ontario Limited"), which is assigned by the provincial or territorial government where the corporation incorporates.

text: In most countries, corporate names include a term or an abbreviation that denotes the corporate status of the entity (for example, "Incorporated" or "Inc." in the United States) or the limited liability of its members (for example, "Limited" or "Ltd."). These terms vary by jurisdiction and language. In some jurisdictions, they are mandatory, and in others they are not.[46] Their use puts everybody on constructive notice that they are dealing with an entity whose liability is limited: one can only collect from whatever assets the entity still controls when one obtains a judgment against it.

text: Some jurisdictions do not allow the use of the word "company" alone to denote corporate status, since the word "company" may refer to a partnership or some other form of collective ownership (in the United States it can be used by a sole proprietorship but this is not generally the case elsewhere).[citation needed]


document_title: Lipopolysaccharide

question_text: when would endotoxins be released from a gram (-) bacterial cell

question_tokens: when would endotoxins be released from a gram ( - ) bacterial cell

root

text: Lipopolysaccharide

text: Discovery[edit]

text: The toxic activity of LPS was first discovered and termed "endotoxin" by Richard Friedrich Johannes Pfeiffer, who distinguished between exotoxins, which he classified as a toxin that is released by bacteria into the surrounding environment, and endotoxins, which he considered to be a toxin kept "within" the bacterial cell and released only after destruction of the bacterial cell wall.[1]:84    Subsequent work showed that release of LPS from gram negative microbes does not necessarily require the destruction of the bacterial cell wall, but rather, LPS is secreted as part of the normal physiological activity of membrane vesicle trafficking in the form of  bacterial outer membrane vesicles (OMVs), which may also contain other virulence factors and proteins.[2]

tag: p

text: Today, the term 'endotoxin' is mostly used synonymously with LPS,[3] although there are a few endotoxins that are not related to LPS, such as the so-called delta endotoxin proteins secreted by Bacillus thuringiensis.

text: Functions in bacteria[edit]

text: LPS is the major component of the outer membrane of Gram-negative bacteria, contributing greatly to the structural integrity of the bacteria, and protecting the membrane from certain kinds of chemical attack. LPS also increases the negative charge of the cell membrane and helps stabilize the overall membrane structure. It is of crucial importance to many Gram-negative bacteria, which die if it is mutated or removed; however, it appears that LPS is nonessential in at least some Gram-negative bacteria, such as Neisseria meningitidis, Moraxella catarrhalis, and Acinetobacter baumannii.[4] LPS induces a strong response from normal animal immune systems. It has also been implicated in non-pathogenic aspects of bacterial ecology, including surface adhesion, bacteriophage sensitivity, and interactions with predators such as amoebae.

text: LPS is required for the proper conformation of Omptin activity; however, smooth LPS will sterically hinder omptins.

text: Composition[edit]

text: It comprises three parts:

text:
O antigen (or O polysaccharide)
Core oligosaccharide
Lipid A

tag: ol

text: O-antigen[edit]

text:
A repetitive glycan polymer contained within an LPS is referred to as the O antigen, O polysaccharide, or O side-chain of the bacteria.
The O antigen is attached to the core oligosaccharide, and comprises the outermost domain of the LPS molecule. The composition of the O chain varies from strain to strain. For example, there are over 160 different O antigen structures produced by different E. coli strains.[5] The presence or absence of O chains determines whether the LPS is considered rough or smooth. Full-length O-chains would render the LPS smooth, whereas the absence or reduction of O-chains would make the LPS rough.[6] Bacteria with rough LPS usually have more penetrable cell membranes to hydrophobic antibiotics, since a rough LPS is more hydrophobic.[7] O antigen is exposed on the very outer surface of the bacterial cell, and, as a consequence, is a target for recognition by host antibodies.

text: Core[edit]

text: The Core domain always contains an oligosaccharide component that attaches directly to lipid A and commonly contains sugars such as heptose and 3-Deoxy-D-manno-oct-2-ulosonic acid (also known as KDO, keto-deoxyoctulosonate).[8] The LPS Cores of many bacteria also contain non-carbohydrate components, such as phosphate, amino acids, and ethanolamine substituents.

text: Lipid A[edit]

text: Lipid A is, in normal circumstances,  a phosphorylated glucosamine disaccharide decorated with multiple fatty acids. These hydrophobic fatty acid chains anchor the LPS into the bacterial membrane, and the rest of the LPS projects from the cell surface. The lipid A domain is responsible for much of the toxicity of Gram-negative bacteria. When bacterial cells are lysed by the immune system, fragments of membrane containing lipid A are released into the circulation, causing fever, diarrhea, and possible fatal endotoxic shock (also called septic shock). The Lipid A moiety is a very conserved component of the LPS.[9] However Lipid A structure varies among bacterial species and Lipid A structure defines an overall host immune activation.[10]

text: Lipooligosaccharides[edit]

text:
Lipooligosaccharides (LOS) are glycolipids found in the outer membrane of some types of Gram-negative bacteria, such as Neisseria spp. and Haemophilus spp. The term is synonymous with the low molecular weight form of bacterial LPS.[11] LOS plays a central role in maintaining the integrity and functionality of the outer membrane of the Gram negative cell envelope.
Lipooligosaccharides play an important role in the pathogenesis of certain bacterial infections because they are capable of acting as immunostimulators and immunomodulators.[11] Furthermore, LOS molecules are responsible for the ability of some bacterial strains to display molecular mimicry and antigenic diversity, aiding in the evasion of host immune defenses and thus contributing to the virulence of these bacterial strains.

text:
Chemically, lipooligosaccharides lack O-antigens and possess only a lipid A-based outer membrane-anchoring moiety, and an oligosaccharide core.[12]  In the case of Neisseria meningitidis, the lipid A portion of the molecule has a symmetrical structure and the inner core is composed of 3-deoxy-D-manno-2-octulosonic acid (KDO) and heptose (Hep) moieties. The outer core oligosaccharide chain varies depending on the bacterial strain.[11][12]
The term lipooligosaccharide is used to refer to the low molecular weight form of bacterial lipopolysaccharides, which can be categorized into two forms: the high molecular weight (Mr, or smooth) form possesses a high molecular weight, repeating polysaccharide O-chain, while the low molecular weight (low-Mr or rough) form, lacks the O-chain but possesses a short oligosaccharide in its place.[11]

text: LPS modifications[edit]

text:
The making of LPS can be modified in order to present a specific sugar structure. Those can be recognised by either other LPS (which enables to inhibit LPS toxins) or glycosyltransferases that use those sugar structure to add more specific sugars.
It has recently been shown that a specific enzyme in the intestine (alkaline phosphatase) can detoxify LPS by removing the two phosphate groups found on LPS carbohydrates.[13]  This may function as an adaptive mechanism to help the host manage potentially toxic effects of gram-negative bacteria normally found in the small intestine. A different enzyme may detoxify LPS when it enters, or is produced in, animal tissues.  Neutrophils, macrophages, and dendritic cells produce a lipase, acyloxyacyl hydrolase (AOAH), that inactivates LPS by removing the two secondary acyl chains from lipid A.  If they are given LPS parenterally, mice that lack AOAH develop high titers of non-specific antibodies, develop prolonged hepatomegaly, and experience prolonged endotoxin tolerance. LPS inactivation may be required for animals to restore homeostasis after parenteral LPS exposure.[14]

text: Biosynthesis and transport[edit]

text: Biological effects on hosts infected with gram-negative bacteria[edit]

text: Immune response[edit]

text: LPS acts as the prototypical endotoxin because it binds the CD14/TLR4/MD2 receptor complex in many cell types, but especially in monocytes, dendritic cells, macrophages and B cells, which promotes the secretion of pro-inflammatory cytokines, nitric oxide, and eicosanoids.[17]

text: As part of the cellular stress response, superoxide is one of the major reactive oxygen species induced by LPS in various cell types that express TLR (toll-like receptor).

text: LPS is also an exogenous pyrogen (fever-inducing substance).

text: Being of crucial importance to Gram-negative bacteria, these molecules make candidate targets for new antimicrobial agents.

text: Some researchers doubt reports of generalized toxic effects attributed to all lipopolysaccharides, in particular, for cyanobacteria.[18]

text:
LPS function has been under experimental research for several years due to its role in activating many transcription factors. LPS also produces many types of mediators involved in septic shock. Humans are much more sensitive to LPS than other animals (e.g., mice). A dose of 1 µg/kg induces shock in humans, but mice will tolerate a dose up to a thousand times higher.[19] This may relate to differences in the level of circulating natural antibodies between the two species.[20][21]
Said et al. showed that LPS causes an IL-10-dependent inhibition of CD4 T-cell expansion and function by up-regulating PD-1 levels on monocytes which leads to IL-10 production by monocytes after binding of PD-1 by PD-L1.[22]

text: Endotoxins are in large part responsible for the dramatic clinical manifestations of infections with pathogenic Gram-negative bacteria, such as Neisseria meningitidis, the pathogens that causes meningococcal disease, including meningococcemia, Waterhouse–Friderichsen syndrome, and meningitis.

text: Bruce Beutler was awarded a portion of the 2011 Nobel Prize in Physiology or Medicine for his work demonstrating that TLR4 is the LPS receptor.[23][24]

text: Portions of the LPS from several bacterial strains have been shown to be chemically similar to human host cell surface molecules; the ability of some bacteria to present molecules on their surface which are chemically identical or similar to the surface molecules of some types of host cells is termed molecular mimicry.[25]  For example, in Neisseria meningitidis L2,3,5,7,9, the terminal tetrasaccharide portion of the oligosaccharide (lacto-N-neotetraose) is the same tetrasaccharide as that found in paragloboside, a precursor for ABH glycolipid antigens found on human erythrocytes.[11] In another example, the terminal trisaccharide portion (lactotriaose) of the oligosaccharide from pathogenic Neisseria spp. LOS is also found in lactoneoseries glycosphingolipids from human cells.[11] Most meningococci from groups B and C, as well as gonococci, have been shown to have this trisaccharide as part of their LOS structure.[11]  The presence of these human cell surface 'mimics' may, in addition to acting as a 'camouflage' from the immune system, play a role in the abolishment of immune tolerance when infecting hosts with certain human leukocyte antigen (HLA) genotypes, such as HLA-B35.[11]

text: Recently, a new study published has discovered that LPS can be sensed directly by hematopoietic stem cells (HSCs) through the bonding with TLR4, causing them to proliferate in reaction to a systemic infection. This response activate the TLR4-TRIF-ROS-p38 signaling within the HSCs and through a sustained TLR4 activation can cause a proliferative stress, leading to impair their competitive repopulating ability.[26] Infection in mice using S. typhimurium showed similar results, validating the experimental model also in vivo.

text: Effect of variability on immune response[edit]

text: O-antigens (the outer carbohydrates) are the most variable portion of the LPS molecule, imparting the antigenic specificity. In contrast, lipid A is the most conserved part. However, lipid A composition also may vary (e.g., in number and nature of acyl chains even within or between genera). Some of these variations may impart antagonistic properties to these LPS. For example, Rhodobacter sphaeroides diphosphoryl lipid A (RsDPLA) is a potent antagonist of LPS in human cells, but is an agonist in hamster and equine cells.[citation needed]

text: It has been speculated that conical Lipid A (e.g., from E. coli) are more agonistic, less conical lipid A like those of Porphyromonas gingivalis may activate a different signal (TLR2 instead of TLR4), and completely cylindrical lipid A like that of Rhodobacter sphaeroides is antagonistic to TLRs.[27][28]

text: LPS gene clusters are highly variable between different strains, subspecies, species of bacterial pathogens of plants and animals.[29][30]

text:
Normal human blood serum contains anti-LOS antibodies that are bactericidal and patients that have infections caused by serotypically distinct strains possess anti-LOS antibodies that differ in their specificity compared with normal serum.[31] These differences in humoral immune response to different LOS types can be attributed to the structure of the LOS molecule, primarily within the structure of the oligosaccharide portion of the LOS molecule.[31]
In Neisseria gonorrhoeae it has been demonstrated that the antigenicity of LOS molecules can change during an infection due to the ability of these bacteria to synthesize more than one type of LOS,[31] a characteristic known as phase variation. Additionally, Neisseria gonorrhoeae, as well as Neisseria meningitidis and Haemophilus influenzae,[11] are capable of further modifying their LOS in vitro, for example through sialylation (modification with sialic acid residues), and as a result are able to increase their resistance to complement-mediated killing [31] or even down-regulate complement activation[11] or evade the effects of bactericidal antibodies.[11] Sialylation may also contribute to hindered neutrophil attachment and phagocytosis by immune system cells as well as a reduced oxidative burst.[11] Haemophilus somnus, a pathogen of cattle, has also been shown to display LOS phase variation, a characteristic which may help in the evasion of bovine host immune defenses.[32]
Taken together, these observations suggest that variations in bacterial surface molecules such as LOS can help the pathogen evade both the humoral (antibody and complement-mediated) and the cell-mediated (killing by neutrophils, for example) host immune defenses.

text: non-canonical pathways of LPS recognition[edit]

text:
Recently, it was shown that in addition to TLR4 mediated pathways, certain members of the family of the transient receptor potential ion channels recognize LPS[33]. LPS-mediated activation of TRPA1 was shown in mice[34] and Drosophila melanogaster flies.[35] At higher concentrations, LPS activates other members of the sensory TRP channel family as well, such as TRPV1, TRPM3 and to some extent TRPM8.[36]
LPS is recognized by TRPV4 on epithelial cells. TRPV4 activation by LPS was necessary and sufficient to induce nitric oxide production with a bactericidal effect.[37]

text: Health effects[edit]

text: Endotoxemia[edit]

text: The presence of endotoxins in the blood is called endotoxemia. It can lead to septic shock, if the immune response is severely pronounced.[38]

text: Moreover, endotoxemia of intestinal origin, especially, at the host-pathogen interface, is considered to be an important factor in the development of alcoholic hepatitis,[39]  which is likely to develop on the basis of the small bowel bacterial overgrowth syndrome and an increased intestinal permeability.[40]

text:
Lipid A may cause uncontrolled activation of mammalian immune systems with production of inflammatory mediators that may lead to septic shock.[12] This inflammatory reaction is mediated by Toll-like receptor 4 which is responsible for immune system cell activation.[12] Damage to the endothelial layer of blood vessels caused by these inflammatory mediators can lead to capillary leak syndrome, dilation of blood vessels and a decrease in cardiac function and can lead to septic shock.[41] Pronounced complement activation can also be observed later in the course as the bacteria multiply in the blood.[41] High bacterial proliferation triggering destructive endothelial damage can also lead to disseminated intravascular coagulation (DIC) with loss of function of certain internal organs such as the kidneys, adrenal glands and lungs due to compromised blood supply. The skin can show the effects of vascular damage often coupled with depletion of coagulation factors in the form of petechiae, purpura and ecchymoses. The limbs can also be affected, sometimes with devastating consequences such as the development of gangrene, requiring subsequent amputation.[41] Loss of function of the adrenal glands can cause adrenal insufficiency and additional hemorrhage into the adrenals causes Waterhouse-Friderichsen syndrome, both of which can be life-threatening.
It has also been reported that gonococcal LOS can cause damage to human fallopian tubes.[31]

text: Auto-immune disease[edit]

text: The molecular mimicry of some LOS molecules is thought to cause autoimmune-based host responses, such as flareups of multiple sclerosis.[11][25]  Other examples of bacterial mimicry of host structures via LOS are found with the bacteria Helicobacter pylori and Campylobacter jejuni, organisms which cause gastrointestinal disease in humans, and Haemophilus ducreyi which causes chancroid. Certain C. jejuni LPS serotypes (attributed to certain tetra- and pentasaccharide moieties of the core oligosaccharide) have also been implicated with Guillain–Barré syndrome and a variant of Guillain–Barré called Miller-Fisher syndrome.[11]

text: Link to obesity[edit]

text: Epidemiological studies have previously shown that increased endotoxin load, which can be a result of increased populations of endotoxin producing bacteria in the intestinal tract, is associated with certain obesity-related patient groups.[42][43][44] Other studies have shown that purified endotoxin from Escherichia coli can induce obesity and insulin-resistance when injected into germ-free mouse models.[45] A more recent study has uncovered a potentially contributing role for Enterobacter cloacae B29 toward obesity and insulin resistance in a human patient.[46] The presumed mechanism for the association of endotoxin with obesity is that endotoxin induces an inflammation-mediated pathway accounting for the observed obesity and insulin resistance.[45] There is a correlation between plasma LPS and insulin resistance.[47]

text: Bacterial genera associated with endotoxin-related obesity effects: Escherichia, Enterobacter

text: Laboratory research and biotechnology production systems[edit]

text: Lipopolysaccharides are frequent contaminants in plasmid DNA prepared from bacteria or proteins expressed from bacteria, and must be removed from the DNA or protein to avoid contaminating experiments and to avoid toxicity of products manufactured using industrial fermentation.[48]

text: Also, ovalbumin is frequently contaminated with endotoxins. Ovalbumin is one of the extensively studied proteins in animal models and also an established model allergen for airway hyper-responsiveness (AHR). Commercially available ovalbumin that is contaminated with LPS can fully activate endothelial cells in an in-vitro assay of the first step of inflammation, and it falsifies research results, as it does not accurately reflect the effect of sole protein antigen on animal physiology.[citation needed]

text: In pharmaceutical production, it is necessary to remove all traces of endotoxin from drug product containers, as even small amounts of endotoxin will cause illness in humans.  A depyrogenation oven is used for this purpose.  Temperatures in excess of 300 °C are required to break down this substance. A defined endotoxin reduction rate is a correlation between time and temperature. Based on primary packaging material as syringes or vials, a glass temperature of 250 °C and a holding time of 30 minutes is typical to achieve a reduction of endotoxin levels by a factor of 1000.[49]

text: The standard assay for detecting presence of endotoxin is the Limulus Amebocyte Lysate (LAL) assay, utilizing blood from the Horseshoe crab (Limulus polyphemus).[50]  Very low levels of LPS can cause coagulation of the limulus lysate due to a powerful amplification through an enzymatic cascade.   However, due to the dwindling population of horseshoe crabs, and the fact that there are factors that interfere with the LAL assay, efforts have been made to develop alternative assays, with the most promising ones being ELISA tests using a recombinant version of a protein in the LAL assay, Factor C.[51]


document_title: You Belong to Me (1952 song)

question_text: who sang the song you belong to me

question_tokens: who sang the song you belong to me

text: You Belong to Me (1952 song)

text: Conception and composition[edit]

text: "You Belong to Me" is credited to three writers: Pee Wee King, Chilton Price and Redd Stewart.

text: Price, a songwriting librarian at WAVE Radio Louisville, had written the song in its virtual entirety as "Hurry Home to Me" envisioning the song as an American woman's plea to a sweetheart serving overseas in World War II. Afforded songwriting credit on the song mostly in exchange for their work in promoting it, King and Stewart did slightly adjust Price's composition musically and lyrically, shifting the focus from a wartime background "into a kind of universal song about separated lovers" and changing the title to "You Belong to Me." Price had previously had success with another hit which she had written, "Slow Poke," under a similar arrangement with the two men.[1][2]

text: History[edit]

text: This article needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. (January 2016) (Learn how and when to remove this template message)

tag: table

text: The first 1952 recording of the song was by Joni James. She had seen the sheet music in the Woods Building in Chicago and the lyrics attracted her. She recorded the song in February, 1952, in Chicago and it was released in March on the local Sharp Records label as her second single on August 5, 1952, after Jo Stafford, Patti Page and Dean Martin had covered it. James' version also was issued on M-G-M Records for national distribution. The best-known early 1952 version of the song was recorded after James' recording by Sue Thompson on Mercury's country label as catalog number 6407.[3] It was soon covered by Patti Page, whose version was issued by Mercury as catalog number 5899, with "I Went to Your Wedding" (a bigger Patti Page hit, reaching No 1) on the flip side. It entered the Billboard chart on August 22, 1952, and lasted 12 weeks on the chart, peaking at No. 4.[4]

text: A cover version by Jo Stafford became the most popular version. Issued by Columbia Records as catalog number 39811, it was Stafford's biggest hit, topping the charts in both the United States and the United Kingdom (the first song by a female singer to top the UK Singles Chart).[5] It first entered the US chart on August 1, 1952 and remained there for 24 weeks.[4] In the UK, it appeared in the first ever UK chart of 14 November 1952 (then a top 12) and reached number 1 on 16 January 1953, being only the second record to top such chart,[5] remaining in the chart for a total of 19 weeks.[6] Another cover version, by Dean Martin, released by Capitol Records as catalog number 2165, was also in play at that time. This version first entered the chart on August 29, 1952, and remained on the chart for 10 weeks, reaching No. 12.[4] All the versions were combined in the rankings on the Cash Box charts, and the song reached No. 1 on those charts as well, lasting on the chart for more than half a year.

text: In 1958, the song crossed over into rock for the first time on the Capitol album Gene Vincent Rocks and the Blue Caps Roll. A later version of the song, by the Duprees, also made the Billboard Top 10, reaching No. 7 in 1962. It was recorded by many other pop vocalists, including Patsy Cline and Bing Crosby. A solo acoustic version was recorded by Bob Dylan for the 1992 album Good as I Been to You but was eventually left off as an out-take; the recording surfaced two years later in the soundtrack for the 1994 film Natural Born Killers.

text: A loop of Jo Stafford's introduction was used by Caviar in "The Good Times Are Over" repeatedly throughout the song.

text: The song has also appeared on many soundtracks. Vonda Shepard's cover was used frequently on the TV series Ally McBeal alongside romantic scenes of Ally McBeal and Billy Thomas. A version by Jason Wade was part of the soundtrack to the 2001 animated film Shrek. Singer Tori Amos also recorded the classic for the Julia Roberts film Mona Lisa Smile in 2003. Actress Rose McGowan sang it on the soundtrack for the Planet Terror segment of the 2007 film Grindhouse. While onscreen, Bette Midler sings a fragment of the song (to Nick Nolte) in the 1986 comedy Down and Out in Beverly Hills.

text: On February 1, 2007, a short rendition of the song was sung by 64-year-old Sherman Pore as an audition piece for the television show American Idol, as a tribute to his wife who had died from cancer two days before.

text: Mary Higgins Clark referenced the song throughout her novel of the same name, which was published by Pocket Books on April 1, 1999.

text: In the British film The Deep Blue Sea (released 2011), directed by Terence Davies, the drinkers in a London pub perform the song which later modulates into Jo Stafford's version.

text: The song was also featured in the 2013 video game BioShock Infinite as part of its Burial at Sea story add-on. In the game the song is performed by the lead character Elizabeth and sung by her voice actress, Courtnee Draper; footage of Draper performing the song in the recording studio is shown during the game's end credits.

text: Annie Lennox recorded a slow, piano-driven version of the song for her 2014 release, Nostalgia.

text: Recorded versions[edit]

text: This section may contain indiscriminate, excessive, or irrelevant examples. Please improve the article by adding more descriptive text and removing less pertinent examples. See Wikipedia's guide to writing better articles for further suggestions.

text:
The Earls
Danny Aiello
Mose Allison
Tori Amos
Paul Anka
Fiona Apple
Gene Austin
Atlas Sound
Pat Boone
Bonnie Bramlett
Michael Bublé
The Alley Cats
Rick Astley
Carla Bruni
Ann Hampton Callaway
Benny Carter & his Orch.
Petula Clark
Patsy Cline
Rosemary Clooney
Alma Cogan
Amie Comeaux
Marshall Crenshaw
Bing Crosby
Mike Curb
Deer Tick
The Duprees
Bob Dylan
Firebirds
Ella Fitzgerald
Flat Duo Jets
Tennessee Ernie Ford
Connie Francis
Stephen Fretwell
Judy Garland
Crystal Gayle
Boris Grebenshchikov
Dan Hicks
Homer and Jethro
Joni James
Eilen Jewell
Pee Wee King
The Lennon Sisters
Peggy Lee
Annie Lennox
Jerry Lee Lewis
Dean Martin
Freddy Martin and His Orchestra Vocal
Johnny Mathis
Gene McDaniels
Maureen McGovern
Rose McGowan
Misfits
Jane Morgan
Anne Murray
OC Times
One AM Radio
The Orioles
Patti Page
Jim Reeves
Kate Rusby
Santo & Johnny
Vonda Shepard
Hank Snow
Jo Stafford
Ringo Starr
Rod Stewart (from the Japanese version of Stardust: The Great American Songbook, Volume III 2004)
Ben Taylor
Sue Thompson
Tommy Tune
Gene Vincent
Jason Wade
Wintergreen
Steve Tran
Courtnee Draper


document_title: Stimulus (physiology)

question_text: what is an example of an internal stimulus

text: Stimulus (physiology)

text: Types[edit]

text: Internal[edit]

text: Homeostatic imbalances[edit]

text: Homeostatic imbalances are the main driving force for changes of the body. These stimuli are monitored closely by receptors and sensors in different parts of the body. These sensors are mechanoreceptors, chemoreceptors and thermoreceptors that, respectively, respond to pressure or stretching, chemical changes, or temperature changes. Examples of mechanoreceptors include baroreceptors which detect changes in blood pressure, Merkel's discs which detect sustained touch and pressure, and hair cells which detect sound stimuli. Homeostatic imbalances that can serve as internal stimuli include nutrient and ion levels in the blood, oxygen levels, and water levels. Deviations from the homeostatic ideal may generate a homeostatic emotion, such as pain, thirst or fatigue, that motivates behavior that will restore the body to stasis (such as withdrawal, drinking or resting).[1]

text: Blood pressure[edit]

text: Blood pressure, heart rate, and cardiac output are measured by stretch receptors found in the carotid arteries. Nerves embed themselves within these receptors and when they detect stretching, they are stimulated and fire action potentials to the central nervous system. These impulses inhibit the constriction of blood vessels and lower the heart rate. If these nerves do not detect stretching, the body determines perceives low blood pressure as a dangerous stimulus and signals are not sent, preventing the inhibition CNS action; blood vessels constrict and the heart rate increases, causing an increase in blood pressure in the body.[2]

text: External[edit]

text: Touch and pain[edit]

text: Sensory feelings, especially pain, are stimuli that can elicit a large response and cause neurological changes in the body. Pain also causes a behavioral change in the body, which is proportional to the intensity of the pain. The feeling is recorded by sensory receptors on the skin and travels to the central nervous system, where it is integrated and a decision on how to respond is made; if it is decided that a response must be made, a signal is sent back down to a muscle, which acts appropriately according to the stimulus.[1] The postcentral gyrus is the location of the primary somatosensory area, the main sensory receptive area for the sense of touch.[3]

text: Pain receptors are known as nociceptors. Two main types of nociceptors exist, A-fiber nociceptors and C-fiber nociceptors. A-fiber receptors are myelinated and conduct currents rapidly. They are mainly used to conduct fast and sharp types of pain. Conversely, C-fiber receptors are unmyelinated and slowly transmit. These receptors conduct slow, burning, diffuse pain.[4]

text: The absolute threshold for touch is the minimum amount of sensation needed to elicit a response from touch receptors. This amount of sensation has a definable value and is often considered to be the force exerted by dropping the wing of a bee onto your cheek from a distance of one centimeter. This value will change based on the body part being touched.[5]

text: Vision[edit]

text: Vision provides opportunity for the brain to perceive and respond to changes occurring around the body. Information, or stimuli, in the form of light enters the retina, where it excites a special type of neuron called a photoreceptor cell. A local graded potential begins in the photoreceptor, where it excites the cell enough for the impulse to be passed along through a track of neurons to the central nervous system. As the signal travels from photoreceptors to larger neurons, action potentials must be created for the signal to have enough strength to reach the CNS.[2] If the stimulus does not warrant a strong enough response, it is said to not reach absolute threshold, and the body does not react. However, if the stimulus is strong enough to create an action potential in neurons away from the photoreceptor, the body will integrate the information and react appropriately. Visual information is processed in the occipital lobe of the CNS, specifically in the primary visual cortex.[2]

text: The absolute threshold for vision is the minimum amount of sensation needed to elicit a response from photoreceptors in the eye. This amount of sensation has a definable value and is often considered to be the amount of light present from someone holding up a single candle 30 miles away, if one's eyes were adjusted to the dark.[5]

text: Smell[edit]

text: Smell allows the body to recognize chemical molecules in the air through inhalation. Olfactory organs located on either side of the nasal septum consist of olfactory epithelium and lamina propria. The olfactory epithelium, which contains olfactory receptor cells, covers the inferior surface of the cribiform plate, the superior portion of the perpendicular plate, the superior nasal concha. Only roughly two percent of airborne compounds inhaled are carried to olfactory organs as a small sample of the air being inhaled. Olfactory receptors extend past the epithelial surface providing a base for many cilia that lie in the surrounding mucus. Odorant-binding proteins interact with these cilia stimulating the receptors. Odorants are generally small organic molecules. Greater water and lipid solubility is related directly to stronger smelling odorants. Odorant binding to G protein coupled receptors activates adenylate cyclase, which converts ATP to camp. cAMP, in turn, promotes the opening of sodium channels resulting in a localized potential.[6]

text: The absolute threshold for smell is the minimum amount of sensation needed to elicit a response from receptors in the nose. This amount of sensation has a definable value and is often considered to be a single drop of perfume in a six-room house. This value will change depending on what substance is being smelled.[5]

text: Taste[edit]

text: Taste records flavoring of food and other materials that pass across the tongue and through the mouth. Gustatory cells are located on the surface of the tongue and adjacent portions of the pharynx and larynx. Gustatory cells form on taste buds, specialized epithelial cells, and are generally turned over every ten days. From each cell, protrudes microvilli, sometimes called taste hairs, through also the taste pore and into the oral cavity. Dissolved chemicals interact with these receptor cells; different tastes bind to specific receptors. Salt and sour receptors are chemically gated ion channels, which depolarize the cell. Sweet, bitter, and umami receptors are called gustducins, specialized G protein coupled receptors. Both divisions of receptor cells release neurotransmitters to afferent fibers causing action potential firing.[6]

text: The absolute threshold for taste is the minimum amount of sensation needed to elicit a response from receptors in the mouth. This amount of sensation has a definable value and is often considered to be a single drop of quinine sulfate in 250 gallons of water.[5]

text: Sound[edit]

text: Changes in pressure caused by sound reaching the external ear resonate in the tympanic membrane, which articulates with the auditory ossicles, or the bones of the middle ear. These tiny bones multiply these pressure fluctuations as they pass the disturbance into the cochlea, a spiral-shaped bony structure within the inner ear. Hair cells in the cochlear duct, specifically the organ of Corti, are deflected as waves of fluid and membrane motion travel through the chambers of the cochlea. Bipolar sensory neurons located in the center of the cochlea monitor the information from these receptor cells and pass it on to the brainstem via the cochlear branch of cranial nerve VIII. Sound information is processed in the temporal lobe of the CNS, specifically in the primary auditory cortex.[6]

text: The absolute threshold for sound is the minimum amount of sensation needed to elicit a response from receptors in the ears. This amount of sensation has a definable value and is often considered to be a watch ticking in an otherwise soundless environment 20 feet away.[5]

text: Equilibrium[edit]

text: Semi circular ducts, which are connected directly to the cochlea, can interpret and convey to the brain information about equilibrium by a similar method as the one used for hearing. Hair cells in these parts of the ear protrude kinocilia and stereocilia into a gelatinous material that lines the ducts of this canal. In parts of these semi circular canals, specifically the maculae, calcium carbonate crystals known as statoconia rest on the surface of this gelatinous material. When tilting the head or when the body undergoes linear acceleration, these crystals move disturbing the cilia of the hair cells and, consequently, affecting the release of neurotransmitter to be taken up by surrounding sensory nerves. In other areas of the semi circular canal, specifically the ampulla, a structure known as the cupula—analogous to the gelatinous material in the maculae—distorts hair cells in a similar fashion when the fluid medium that surrounds it causes the cupula itself to move. The ampulla communicates to the brain information about the head’s horizontal rotation. Neurons of the adjacent vestibular ganglia monitor the hair cells in these ducts. These sensory fibers form the vestibular branch of the cranial nerve VIII.[6]

text: Cellular response[edit]

text: In general, cellular response to stimuli is defined as a change in state or activity of a cell in terms of movement, secretion, enzyme production, or gene expression.[7] Receptors on cell surfaces are sensing components that monitor stimuli and respond to changes in the environment by relaying the signal to a control center for further processing and response. Stimuli are always converted into electrical signals via transduction. This electrical signal, or receptor potential, takes a specific pathway through the nervous system to initiate a systematic response. Each type of receptor is specialized to respond preferentially to only one kind of stimulus energy, called the adequate stimulus. Sensory receptors have a well-defined range of stimuli to which they respond, and each is tuned to the particular needs of the organism. Stimuli are relayed throughout the body by mechanotransduction or chemotransduction, depending on the nature of the stimulus.[2]

text: Mechanical[edit]

text: In response to a mechanical stimulus, cellular sensors of force are proposed to be extracellular matrix molecules, cytoskeleton, transmembrane proteins, proteins at the membrane-phospholipid interface, elements of the nuclear matrix, chromatin, and the lipid bilayer. Response can be twofold: the extracellular matrix, for example, is a conductor of mechanical forces but its structure and composition is also influenced by the cellular responses to those same applied or endogenously generated forces.[8] Mechanosensitive ion channels are found in many cell types and it has been shown that the permeability of these channels to cations is affected by stretch receptors and mechanical stimuli.[9] This permeability of ion channels is the basis for the conversion of the mechanical stimulus into an electrical signal..

text: Chemical[edit]

text: Chemical stimuli, such as odorants, are received by cellular receptors that are often coupled to ion channels responsible for chemotransduction. Such is the case in olfactory cells.[10] Depolarization in these cells result from opening of non-selective cation channels upon binding of the odorant to the specific receptor. G protein-coupled receptors in the plasma membrane of these cells can initiate second messenger pathways that cause cation channels to open.

text: In response to stimuli, the sensory receptor initiates sensory transduction by creating graded potentials or action potentials in the same cell or in an adjacent one. Sensitivity to stimuli is obtained by chemical amplification through second messenger pathways in which enzymatic cascades produce large numbers of intermediate products, increasing the effect of one receptor molecule.[2]

text: Systematic response[edit]

text: Nervous-system response[edit]

text: Though receptors and stimuli are varied, most extrinsic stimuli first generate localized graded potentials in the neurons associated with the specific sensory organ or tissue.[6] In the nervous system, internal and external stimuli can elicit two different categories of responses: an excitatory response, normally in the form of an action potential, and an inhibitory response.[11] When a neuron is stimulated by an excitatory impulse, neuronal dendrites are bound by neurotransmitters which cause the cell to become permeable to a specific type of ion; the type of neurotransmitter determines to which ion the neurotransmitter will become permeable. In excitatory postsynaptic potentials, an excitatory response is generated. This is caused by an excitatory neurotransmitter, normally glutamate binding to a neuron's dendrites, causing an influx of sodium ions through channels located near the binding site.

text: This change in membrane permeability in the dendrites is known as a local graded potential and causes the membrane voltage to change from a negative resting potential to a more positive voltage, a process known as depolarization. The opening of sodium channels allows nearby sodium channels to open, allowing the change in permeability to spread from the dendrites to the cell body. If a graded potential is strong enough, or if several graded potentials occur in a fast enough frequency, the depolarization is able to spread across the cell body to the axon hillock. From the axon hillock, an action potential can be generated and propagated down the neuron's axon, causing sodium ion channels in the axon to open as the impulse travels. Once the signal begins to travel down the axon, the membrane potential has already passed threshold, which means that it cannot be stopped. This phenomenon is known as an all-or-nothing response. Groups of sodium channels opened by the change in membrane potential strengthen the signal as it travels away from the axon hillock, allowing it to move the length of the axon. As the depolarization reaches the end of the axon, or the axon terminal, the end of the neuron becomes permeable to calcium ions, which enters the cell via calcium ion channels. Calcium causes the release of neurotransmitters stored in synaptic vesicles, which enter the synapse between two neurons known as the presynaptic and postsynaptic neurons; if the signal from the presynaptic neuron is excitatory, it will cause the release of an excitatory neurotransmitter, causing a similar response in the postsynaptic neuron.[2] These neurons may communicate with thousands of other receptors and target cells through extensive, complex dendritic networks. Communication between receptors in this fashion enables discrimination and the more explicit interpretation of external stimuli. Effectively, these localized graded potentials trigger action potentials that communicate, in their frequency, along nerve axons eventually arriving in specific cortexes of the brain. In these also highly specialized parts of the brain, these signals are coordinated with others to possibly trigger a new response.[6]

text: If a signal from the presynaptic neuron is inhibitory, inhibitory neurotransmitters, normally GABA will be released into the synapse.[2] This neurotransmitter causes an inhibitory postsynaptic potential in the postsynaptic neuron. This response will cause the postsynaptic neuron to become permeable to chloride ions, making the membrane potential of the cell negative; a negative membrane potential makes it more difficult for the cell to fire an action potential and prevents any signal from being passed on through the neuron. Depending on the type of stimulus, a neuron can be either excitatory or inhibitory.[12]

text: Muscular-system response[edit]

text: Nerves in the peripheral nervous system spread out to various parts of the body, including muscle fibers. A muscle fiber and the motor neuron to which it is connected.[13] The spot at which the motor neuron attaches to the muscle fiber is known as the neuromuscular junction. When muscles receive information from internal or external stimuli, muscle fibers are stimulated by their respective motor neuron. Impulses are passed from the central nervous system down neurons until they reach the motor neuron, which releases the neurotransmitter acetylcholine (ACh) into the neuromuscular junction. ACh binds to nicotinic acetylcholine receptors on the surface of the muscle cell and opens ion channels, allowing sodium ions to flow into the cell and potassium ions to flow out; this ion movement causes a depolarization, which allows for the release of calcium ions within the cell. Calcium ions bind to proteins within the muscle cell to allow for muscle contraction; the ultimate consequence of a stimulus.[2]

text: Endocrine-system response[edit]

text: Vasopressin[edit]

text: The endocrine system is affected largely by many internal and external stimuli. One internal stimulus that causes hormone release is blood pressure. Hypotension, or low blood pressure, is a large driving force for the release of vasopressin, a hormone which causes the retention of water in the kidneys. This process also increases an individuals thirst. By fluid retention or by consuming fluids, if an individual's blood pressure returns to normal, vasopressin release slows and less fluid is retained by the kidneys. Hypovolemia, or low fluid levels in the body, can also act as a stimulus to cause this response.[14]

text: Epinephrine[edit]

text: Epinephrine, also known as adrenaline, is also used commonly to respond to both internal and external changes. One common cause of the release of this hormone is the Fight-or-flight response. When the body encounters an external stimulus that is potentially dangerous, epinephrine is released from the adrenal glands. Epinephrine causes physiological changes in the body, such as constriction of blood vessels, dilation of pupils, increased heart and respiratory rate, and the metabolism of glucose. All of these responses to a single stimuli aid in protecting the individual, whether the decision is made to stay and fight, or run away and avoid danger.[15][16]

text: Digestive-system response[edit]

text: Cephalic phase[edit]

text: The digestive system can respond to external stimuli, such as the sight or smell of food, and cause physiological changes before the food ever enters the body. This reflex is known as the cephalic phase of digestion. The sight and smell of food are strong enough stimuli to cause salivation, gastric and pancreatic enzyme secretion, and endocrine secretion in preparation for the incoming nutrients; by starting the digestive process before food reaches the stomach, the body is able to more effectively and efficiently metabolize food into necessary nutrients.[17] Once food hits the mouth, taste and information from receptors in the mouth add to the digestive response. Chemoreceptors and mechanorceptors, activated by chewing and swallowing, further increase the enzyme release in the stomach and intestine.[18]

text: Enteric nervous system[edit]

text: The digestive system is also able to respond to internal stimuli. The digestive tract, or enteric nervous system alone contains millions of neurons. These neurons act as sensory receptors that can detect changes, such as food entering the small intestine, in the digestive tract. Depending on what these sensory receptors detect, certain enzymes and digestive juices from the pancreas and liver can be secreted to aid in metabolism and breakdown of food.[2]

text: Methods and techniques[edit]

text: Clamping techniques[edit]

text: Intracellular measurements of electrical potential across the membrane can be obtained by microelectrode recording. Patch clamp techniques allow for the manipulation of the intracellular or extracellular ionic or lipid concentration while still recording potential. In this way, the effect of various conditions on threshold and propagation can be assessed.[2]

text: Noninvasive neuronal scanning[edit]

text: Positron emission tomography (PET) and magnetic resonance imaging (MRI) permit the noninvasive visualization of activated regions of the brain while the test subject is exposed to different stimuli. Activity is monitored in relation to blood flow to a particular region of the brain.[2]

text: Hindlimb withdrawal time[edit]

text: Sorin Barac et al. in a recent paper published in the Journal of Reconstructive Microsurgery monitored the response of test rats to pain stimuli by inducing an acute, external heat stimulus and measuring hindlimb withdrawal times (HLWT).[19]